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Published on: June 16, 2011
Difference in susceptibility to MxA protein between a coxsackievirus B1 isolate and prototype, impact of serial cell
Wassim Chehadeh1, Hayfaa A Abdulkareem
1Faculty of Medicine, Virology Unit, Department of Microbiology, Kuwait University, Safat, Kuwait. wchehadeh@hsc.edu.kw
Abstract:
Human enteroviruses (EVs) cause a broad spectrum of acute and chronic diseases including meningitis and myocarditis. The type I interferon-induced MxA protein has been shown to inhibit the replication of an EV, coxsackievirus B4 (CVB4), but not cardioviruses such as encephalomyocarditis virus and mengo virus, members of the Picornaviridae family. EVs consist of more than 60 distinct serotypes against which the antiviral activity of MxA was not investigated yet. The main aim of this study was to explore the antiviral activity of MxA protein against a clinical CVB1 isolate and other EV prototypes. Vero cells expressing constituvely MxA protein were infected with EVs, and the percentage of inhibiton of expression of enteroviral RNA and capsid VP1 protein was determined. Following infection of MxA-transfected Vero cells with EVs, the expression of enteroviral RNA was inhibited by up to 99%, and that of VP1 protein by up to 85%. However, there was a difference in the percentage of MxA inhibition of EV replication between the different EV prototypes. This difference in MxA sensitivity was not due to a difference in the viral replication rates. The MxA protein was inactive against the clinical CVB1 isolate, and the replication rate of CVB1 isolate in MxA-transfected Vero cells was higher than that in mock-transfected Vero cells. A serial passage of the clinical CVB1 isolate and other EV prototypes resulted in an increase in their susceptibility to MxA protein. These results suggest the presence of MxA-resistant EV variants that may escape innate immunity and cause disease. J. Med. Virol. 82:424-432, 2010. (c) 2010 Wiley-Liss, Inc.
Insights
The MxA protein inhibits enterovirus (EV) replication, but resistance varies among EV types. Some EV variants, like coxsackievirus B1, can evade MxA, potentially impacting innate immunity during infection.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Human enteroviruses (EVs) cause significant diseases, including meningitis and myocarditis.
- The MxA protein, induced by type I interferon, inhibits some viruses but its activity against diverse EV serotypes is unknown.
- Picornaviridae family members like encephalomyocarditis virus and mengo virus are not inhibited by MxA.
Purpose of the Study:
- To investigate the antiviral activity of the MxA protein against various enterovirus prototypes, including a clinical coxsackievirus B1 isolate.
- To determine the extent of MxA-mediated inhibition of enteroviral RNA and VP1 protein expression.
Main Methods:
- Vero cells constitutively expressing MxA protein were infected with different EV prototypes.
- Enteroviral RNA and capsid VP1 protein expression levels were quantified to assess inhibition.
- Serial passages of EV isolates in MxA-expressing cells were performed to evaluate changes in susceptibility.
Main Results:
- MxA protein inhibited EV RNA expression by up to 99% and VP1 protein by up to 85% in infected Vero cells.
- Significant variation in MxA inhibition was observed among different EV prototypes, not linked to replication rates.
- MxA was inactive against a clinical coxsackievirus B1 isolate, which replicated more efficiently in MxA-expressing cells.
- Serial passage increased the susceptibility of EV prototypes to MxA, suggesting adaptation.
Conclusions:
- MxA protein exhibits differential antiviral activity against various enterovirus serotypes.
- The existence of MxA-resistant EV variants capable of evading innate immunity is suggested.
- These findings highlight potential mechanisms by which enteroviruses may overcome host antiviral defenses and cause disease.
